Acute respiratory disease and chronic bronchitis are present in 10% to 25% of the urban population. Inhaled substances and microbiologic infections are major factors in the genesis of chronic bronchitis. The Secretory Immune System provides the first line of defense against these factors by blocking the passage of some of these agents and prevention of adherence of bacteria to mucosal epithelia, thus protecting the exposed mucosal surfaces. In this project, we intend to prove that there is a generalized secretory immune system protecting the lung with IgA producing B-cells which originate in the gut associated lymphoid tissue (GALT), and which are capable of homing to the respiratory mucosa and other secretory tissues and differentiating tnto IgA secretory plasma cells. We also propose that antigen as well as tissue factors are involved in the homing mechanism. In order to test these hypotheses, we propose to answer the following questions using mice as a model system. (1) Do IgA producing B-cells migrate to the respiratory mucosa under certain inflammatory conditions or to specific or nonspecific antigenic challenge? (2) Do some IgA bearing lymphocytes and epithelial cells in the target tissues have surface recognition factors involved in the homing response? We have obtained preliminary evidence which suggests that antigen can stimulate an IgA secretory response at a distant site and that there exists a specific binding mechanism between IgA lymphoblasts and certain epithelial mucosal cells. For example, we have found that isolated intestinal epithelial cells rosette preferentially with IgA bearing lymphoblasts derived from mesenteric lymph nodes. In related experiments these IgA bearing lymphoblasts bind preferentially to epithelial cells when incubated with thin sections of intestine. These experiments will be repeated with bronchial tissues. These cellular adhesion assays, as well as the proposed homing studies provide the means of testing for the presence of specific cell surface recognition factors, and thus, we propose to isolate the putative factors.